Anti-prion activity of cellulose ether is impaired in mice lacking pre T-cell antigen receptor α, T-cell receptor δ, or lytic granule function
•Immune system roles in the anti-prion action of cellulose ether (CE) are unknown.•CE effect is impaired by pre T-cell antigen receptor α deficiency or thymectomy.•CE effect is also impaired by TCRδ deficiency or lytic granule dysfunction.•The αβ T-cell lineage, B cells or TLR4 signaling pathway do...
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Veröffentlicht in: | International immunopharmacology 2022-06, Vol.107, p.108672-108672, Article 108672 |
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Sprache: | eng |
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Zusammenfassung: | •Immune system roles in the anti-prion action of cellulose ether (CE) are unknown.•CE effect is impaired by pre T-cell antigen receptor α deficiency or thymectomy.•CE effect is also impaired by TCRδ deficiency or lytic granule dysfunction.•The αβ T-cell lineage, B cells or TLR4 signaling pathway do not affect CE effect.•Interaction between NKT and γδ T cells may be involved in the action of CE.
The anti-prion activity of cellulose ether (CE) has been reported in rodents, but the mechanism of action is not well understood. As defects in early T-cell development have been reported in Tga20 mice which show only a slight effect of CE administration, we investigated the involvement of immune functions in the CE action. We confirmed an insertion of the prion protein transgene into the pre T-cell antigen receptor α gene of Tga20 mice, and its impaired expression in the thymus and other tissues. The influence of immune suppression on the CE effect was then examined in high CE-responder mice treated with immunosuppressive agents or neonatal thymectomy. As neonatal thymectomy significantly reduced the CE effect, we compared the influence of various T-cell defects in mice with similar genetic backgrounds. The CE effect was increased or unchanged in mice with defects in the αβ T-cell lineage, whereas it was abolished in T-cell receptor δ deficient mice. Further, when other immune defects were examined, the CE effect was reduced in mice with lysosomal trafficking dysfunction, but was unchanged in mice deficient in B-cell differentiation or toll-like receptor 4 signaling. These findings collectively suggest that the mechanism of CE action may involve γδ T cells and lytic granule function, as well as immune factors like natural killer T cells which are lacking in pre T-cell antigen receptor α deficient mice and neonatally thymectomized mice. |
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ISSN: | 1567-5769 1878-1705 |
DOI: | 10.1016/j.intimp.2022.108672 |